Delicate granular deposits of immune reactants (antibody and complement components) are found by direct immunofluorescence in a high percentage of biopsy specimens of diseased skin. The size and morphology of these deposits correspond to the appearance of immune complexes in the tissue of animals undergoing serum sickness reactions. Recently, we have identified immune reactants at the junction of the epidermis and dermis in patients with atopic dermatitis or lodged in the walls of the microvasculature in erythema multiforme. We propose to study further these, and other, cutaneous diseases in order to better understand their pathogenesis. The presence and composition of antibody and complement components (Clq, C4, C3, C8, C5-9 neoantigen and factor B) will be ascertained by direct immunofluorescence. The cutaneous deposits will be compared and correlated with the presence of circulating immune complexes in the serum of Raji cell immunofluorescence, Raji cell radioimmunoassay or Clq binding by the polyethylene glycol precipitation technique (Clq-PEG). Existing tests will be modified in order to identify immune complexes associated with IgM or IgA globulins which occur in erythema multiforme or dermatitis herpetiformis, respectively. In many patients, recurrent Herpesvirus hominis (HSV) precedes the development of erythema multiforme by 4-10 days. By obtaining serial serum specimens, it should be possible to detect new immune complexes first in the serum and later in the cutaneous lesions. Thus this model is suitable for a dynamic study of a common allergic process in man. Moreover, we will attempt to identify HSV antigens or virions in association with the circulating complexes or in the skin deposits by immunofluorescence or transmission electron microscopy. We believe this work will be a prototype for the study of skin diseases such as allergic angiitis or allergic (atopic) dermatitis.